Arylethanolamines derived from salicylamide with .alpha.- and .beta.-adrenoceptor blocking activities. Preparation of labetalol, its enantiomers and related salicylamides

Abstract

A series of phenethanolamines based on salicylamide was prepared and possessed .beta.-adrenergic blocking properties. When the basic N atom was substituted by some aralkyl groups, the compounds also blocked .alpha.-adrenoceptors. The 1-methyl-3-phenylpropyl derivative labetalol is antihypertensive in rats, dogs and man, and syntheses of its 4 stereoisomers are described. The enantiomer with the R configuration at both asymmetric centers possessed most of the .beta.-blocking activity but little .alpha.-blocking activity. That, with the S configuration at the alcoholic carbon and the R configuration on the amino substituent, is predominantly an .alpha.-adrenoceptor blocking agent.